Amino ketones and method of making



Patented Nov. 7,1939

4 UNITED STAT-ES,

AMINO KETONES AND mrrnon or MAKING Ralph A. Jacobson, Wilmington, Del, assignor to E. I. du Pont de Nemours & Company, Wilmington, De l., a'corporation of Delaware No Drawing. Application April 22, 1936,

- Serial No. 75,749 1 21 Claims. (oi. 260-584) This invention relates to new compositions of matter, more particularly aminoketones, and to processes for their preparation. More specifically it relates to beta-aminoketones formed by reacting a ketone having an isopropyl group with formaldehyde and a. hydrohalide of ammonia or a primary or secondary amine. These types of nitrogen compounds are referredto collectively, for the purposes of this invention, as aminonitrogen compounds having at least one hydrogen atom attached to the amino nitrogen.

This invention has as its object the preparaphase. Unchanged reactants are then removed by separating any remaining upper layer and extracting the residue with ether. The purified residue is then made alkaline with aqueous caustic alkali, the alkaline mixture again extracted with ether, and the aminoketone or ketones obtained by fractionally distilling this second extract. In many cases, as noted below, the reaction product will contain, in addition to. a comparatively low-boiling monomeric betaaminoketone, a relatively high-boiling dimer thereof and in some instances small amounts of trimers or even higher polymers.

Any ketone may be utilized according to this invention in which an isopropyl group is attached to the ketone carbonyl group, i. e.,, compounds of the type RCOCI-HCHa) 2, where R is any hydrocarbon radical; R may be, for example, an

- alkyl, cycloalkyl, aryl, or aralkyl group, particuar examplesof such groups being methyl, ethyl, isopropyl, butyl, cyclohexyl, phenyl, and benzyl.

The aminocompounds used most advantageously in this invention may be represented by :tioned types, or in which R1 and R2 together.

form a divalent hydrocarbon radical. Thus, for

under the above formula which are satisfactory 10' for use in this invention are monoand diethanolamines, amino nitrlles, amino acids, and tion of new monomeric and polymeric betathe'like.

The hydrohalides of ammonia and volatile amines should ordinarily be used in the present 15 process though the use of ammonia or the free amine is not precluded if proper precautions are taken to prevent undue loss by volatllization.

-As will be evident from the examples given hereinafter, ordinary 37% aqueous formaldehyde is preferred for use in this invention, but

paraformaldehyde, hexamethylenetetramine, trioxymethylene or the like can be substituted therefor if suitable solvents, such as ethanol, propanol, butanol, ethyl acetate, butyl acetate 5 and the like, are employed. I

The, nature of the products which are obtained depends upon .conditions of reaction and thecharacter of the reactants. The lower boiling fractions obtained are probably beta-aminoo ketones formed by condensation of a ketone having an isopropyl group with aminomethanols or N-alkylaminomethanols, which are in turn formed by reaction between formaldehyde and ammonia or the amine. The probable reactions may be represented as follows, R, R1, and R: having the previously given definitions:

a, R1 1 ncno nornon 40 R1\, V a I 2 nomon+nooomonm o I rooiowmnonm +rn0' When, in the compound noo.o cm ..oum

R1 is hydrogen, further addition with formaldehyde may occur, as follows:

In some cases, when the group R contains a sufficiently reactive hydrogen atom attached to the carbon atom alpha to the keto carbonyl group (e. g. where R is iso-propyl),' the product of Equation 3 may react with that of Equation 2 to form a dimer, thus:

These dimers, when present in the reaction mixture, constitute fractions of considerably higher boiling points than the monomers from which they are derived, and the two may therefore be readily separated by fractional distillation.

It will be obvious from the foregoing description that dimers cannot be formed when secondary amines are used in the process, for such amines condense with formaldehyde and the than to form compounds of the type The invention may be illustrated by the following examples:

Exnmmr: 1.-Condensati0n of dzisozrropyl Icetone,

formaldehyde, and methylamine lowed to stand for approximately three days at room temperature. It was then extracted with ether to remove unchanged diisopropyl ketone (9 grams). The residual mixture was made alkaline with potassium hydroxide solution, ex-

. tracted several times with ether, and the ether extract dried with magnesium sulfate and distilled. Two products were obtained boiling respectively at under 18 mm. pressure (13 grams) and at under 3.5 mm. pressure (111 grams). The compounds were both strongly basic andreadily soluble in dilute hydrochloric acid solution. Elementary analysis of the lowboiling product showed that it had the correct nitrogen content for the p-aminoketone (CH3) 2CHCOC (CH3) zCHzNI-ICH:

(compare Equation 2). The theoretical per cent nitrogen is 8.91% and the amount found was 9.19%. The index of refraction was 1.4350.

Elementary analysis of the high-boiling fraction was as follows: C, 70.08%; H, 11.67%; N,

wtttllowwwowwoo ill t l m tormula r The low-boiling product proved to be a mixture of the aminoketones: (a)

(CH3) 2CHCOC (CHa) aCHzNH-z V and (b) (CH3)2CHCOC(CH2)2CH2NHCH:, the methyl amine necessary for the formation of (h) originating from the reaction of formaldehyde and ammonium chloride. The high-boiling product (1)) was a dimer of ((1) having the (CH3) 2CHCOC (CH3) 2CHzNI-I- Both (a) and (b) were strongly basic and read- 15 ily soluble in dilute hydrochloric acid solution.

% nitrogen, the theoretical being 9.4%.

Analysis showed that the low-boiling product (a) contained 9.41% nitrogen as compared with' a theoretical nitrogen content of 9.79%, and that the high-boiling product (1)) contained 8.81%

Exanrm 3.-Repetition of Example 2 withoutagitation Example 2 was repeated except that the reaction mixture was not stirred during the course of the reaction. The lowand high-boiling reaction products which were obtained yielded the same analytical and physical data as those described in Example 2. Approximately equal proportions by weight, however, of the two products were obtained in contradistinction to a preponderant amount of high-boiling product when proceeding as described in Example 2.

ExaMPLn 5.-'Conde-nsation of diisopropyl ketone,

dimethylomine hydrochloride, and formaldehy e A mixture of 171 grams (1.5 moles) of diisopropyl lretone, 122 grams (1.5'm oles) of dimethylamine hydrochloride, and 432 grams (5.3 moles) of 37% aqueous formaldehyde solution was gently refluxed and stirred vigorously for 93% hours.

, The upper layer (unreacted ketone) was separated. The lower layer was extracted with ether and the extractions added to the separated upper layer. The ether solution was dried and distilled to recover the unreacted ketone (151 grams). The remainder of the reaction mixture was made alkaline with 30% potassium hydroxide solutionand extracted twice with ether. The ether extract was dried for several hours with magnesium sulfate. After removal of the ether, the

crude product was fractionally distilled and yielded the following main fraction: 10 grams of a liquid boiling at 81-83 C. at 14 mm,

1Wg=1.'4ss8 Y This product proved to be isopropyl dimethylaminomethylisopropyl ketone' wmnorrcomcno 2CH2N(CI'13)2 a strongly basic compound readily soluble in dilute J hydrochloric acid solution. Analysis showed that the product contained 8.06% nitrogen as compared with a theoretical nitrogen content of 3.19%. The yield was 31.12% of the theoretical, based upon the amount of discpropyl ketone which had reacted.

Exmts 6.ndensatiou of dfisopropyl ketone, diethylamine hydrochloride, and formulae A mixture of 114 grams (1 niole) of diisopropyl ketone, 73 grams (1 mole) of diethylamine, 98 grams (1 mole) of concentrated hydrochloric acid (37.5% i and 287 grams (3.5 moles) of 37% aqueous formaldehyde solution was gently refluxed and vigorously stirred for 67 hours. The upper layer (unreacted ketone) was separated. The lower layer was extracted with ether and the extractions added to the separated upper layer;

this solution was dried and distilled to recover the unreacted ketone (61 g. The remainder of the reaction mixture was made alkaline with 30% potassium hydroxide solution and extracted twice with ether. The etherextracts were combined and dried overnight with magnesium 'sul-. fate. After removal of the ether, the crude productfwas fractionally distilled and yielded the following main fraction: 37 grams of a liquid boiling at 100-402 C. at 12 mm,

This product proved to be diethylaminomethyl diisopropyl ketone of the formula a strongly basic compoundreadily soluble in dilute aqueous hydrochloric acid. The yield of the product was 40% of the theoretical based upon the diisopropyl ketone which had reacted. Analysis showed that the product contained 7.48%-

con'tent of 7.04%.

Exaiurm -7.-'-Condensatiort of methyl isopropyl kettme, methylamine hydrochloride, and formaldehyde r A mixture of 51 grams (0.50 mole) of methyl nitrogen as compared with a theoretical nitrogen isopropyl ketone, 40 grains (0.50 mole) of methylamine hydrochloride, and 170 grams (2.1 moles) of 37% aqueous formaldehyde solution was refluxed gently and'stirred vigorously for 8 hours.

The homogeneous solution was extracted with ether to remove unchanged methyl isopropyl ketone (4 grams). action mixture was made alkaline with 30% potassium hydroxide solution and extracted twice with ether. The ether extracts were combined The remainder of the reand driedovernight with magnesium sulfate.

After removal of the ether, the crude product was fractionally distilled and yielded, as the main product, a liquid boiling in the range -111 C. at 15 mm this traction on redistillation gave 27 grams of' a beta-methylamino ketone boiling at M -76 C. at 3 mm.,

Analysis showed 11.15% nitrogen as compared with a theoretical nitrogen content of 10.85% for a compound or the formula CHaCOCKCHa) 2CH2NHCH3. The yield was 38% of the theoretical based on the methyl isopropyl ketone which had reacted. The prodact was strongly basic and readily soluble in dilute aqueous hydrochloric acid.

that the product contained EXAMPLE 8.C'ondensation of mimedketones (obtained as by-product from methanol synthesis), ammonium chloride, and formaldehyde A mixture of 500 grams (4.? moles) of mixed ketones (consisting mainly of ethyl isopropyl and diisopropyl ketones and obtained as a by-product of the synthesis of methanol by catalytic hydrogenation of carbon oxide), 237 grams (4.4 moles) of ammonium chloride, and 1315 grams (16.2 moles) of 37% aqueous formaldehyde was gently refluxed without stirring for 56 hours. The upper layer (unreacted ketones) was separated and the lower layer extracted with ether, the extractions being added to the separated upper layer. The ether solution was distilled to recover the unreacted ketones (104 grams). The remainder of the reaction mixture was made alkaline with 30% potassium hydroxide solution and extracted twice with ether. The ether extracts were combined and dried overnight with magnesium sulfate. After removal of the ether, the crude product was fractionally distilled and yielded the following three main fractions: (0) 131 grams of a liquid boiling in the range 60-78" C. at 12 mm., (b) 92 grams of a liquid boiling in the range 78-113 C. at 12 mm.,

and (c) 97 grams of a liquid boiling in the range 114-172 C. at 12.5 mm. The total weight ofthe fraction was 320 grams. The products were strongly basic and readily soluble in dilute hydrochloric acid solution.

The. proportions of ketone, formaldehyde and amino compounds to be used in this invention may be varied over a considerable range, depending upon the products desired, the relative cost of the reactants, etc. From the considerations already set forth it is clear that, to obtain the monomeric beta-aminoketones described, at least one moleof amino compound andone mole of formaldehyde should be employed per mole of ketone. To obtain the dimeric reaction products described, an excess of formaldehyde is required, that is, the molal ratio of formaldehydezamino compoundzketone should be at least 1.51121. AS will be seen from'the examples, even larger excesses of formaldehyde are preferable if maximum amounts of dimer are to be obtained. An excess of amine over the theoretical 1:1 mole 7 ratio of amine to ketone not only does no harm,

but often promotes better yields by insuring the presence of suflicient aminomethanol or substituted aminomethanol to combine with all of the ketone present. The use of excess amine is particularly advantageous and important when the amine is very volatile and when it isused as such rather than as the hydrohalide. If it is desired to conserve amine rather than ketone, however, any mole ratio may be employed.

Reaction temperatures vary somewhat with the nature and proportions of the reactants, and cannot therefore be set at any arbitrary point, although as a general rule, reaction temperatures in this invention need not exceed about -125" C. Higher or lower temperatures may, however, be employed, particularly (in case of the former) if the reactions are carried out at super-atmospheric pressures.

The duration of the reactions described herein varies with the temperature and other conditions of the reaction. Generally the primary amine hydrohalides react much more rapidly and completely than the secondary amine hydrohalides. Thus, dimethylamine hydrochloride and diethylamine hydrochloride require a much longer period for reaction with diisopropyl ketone and formaldehyde than methylamine hydrochloride requires. A convenient general rule to follow in the case of the primary amines is to allow the reaction to proceed until all the ketone has gone into solution in the reaction mixture. With secondary amines, however, it is often necessary to separate the unreacted ketone and treat the latter with a new supply of formaldehyde and the amine. Longer reaction periods will usually increase the yieldssomewhat and are in no case disadvantageous.

The monomeric beta-aminoketon'es produced by this invention, either alone or modified with other substances, find use as plasticizers, solvents, and the like, for cellulose derivatives, especially cellulose acetate, andnatural and synthetic resins, oils, fats, waxes and the like. They are particularly useful as solvents inasmuch as they combine the solvent power of both ketones and amines. 'They are also useful as alcohol denaturants. The high boiling dimeric products are useful as plasticizers for synthetic resins and cellulose derivatives.

The process described herein has the distinct advantage over somewhat similar processes previously proposed in that it affords a very simple and inexpensive means of providing in a pure state new and useful compositions of matter, such, particularly, as the dimeric betaaminoketones. The process is particularly advantageous in its application to diisopropyl ketone, with which ketone it is very clear cut and gives only monomers and dimers in good yields without attendant formation of more complex polymers. Diisopropyl ketone is considered to be unique in this respect and different in kind from the ketones employed in the prior art since it "is a symmetrical ketone having only one hydrogen atom on the carbon atoms adjacent to the carbonyl group. Ketones such as acetone, methyl ethyl ketone and the like have a multiplicity of alpha-hydrogen atoms on both carbons adjacent to the carbonyl group and for this reason yield a complicated mixture of polymeric products, the separation and identification of which is difficult if not impossible.

Various changes may be made in the methods hereinbefore described without departingfrom the invention or sacrificing any of the advantages thereof.

I claim:

1. The process of preparing amino ketones which comprises reacting a compound having the structural formula i (CHa)iCHCR wherein R is a hydrocarbon radicle, with formaldehyde and a hydrohalide of a compound having a single amino nitrogen atom, said atom being trivalent and attached to at least one hyiii anionic dronen and otherwise joined .onlyto hydrocarbon 9. Process as set forth in claim 2 in which the radicles. hetone is di-isopropyl hetone.

Ki. Amino ketones chtained by reacting a com-' pound having the structural formula (onmcnr in wherein R is a hydrocarbon radicie, with formaldehyde and a compound having a single amino nitrogen atom, said atom neing trivalent and attached to at least one hydrogen and otherwise joined only to hydrocarhon radicles. j

d. Amino lretones obtained by reacting a comnound having the structural lormula (CHEMCHGR wherein R is a hydrocarbon radicle, with iormaldehyde and a hydrohalide of a compound having a single amino nitrogen atom, said atom be- 1 ins trivalent and attached to at least one hytill line trivalent and attached to at least one hy- 45 wherein l't'is a hydrocarbon radicle, with form-' aldehyde, and a substance selected irom they drocen and otherwise joined only to hydrocarbon radicles.

5. amino hetones obtained by reacting with vigorous agitation a mixture of a compound having the structural iormula (GHshCHgR wherein R is a hydrocarbon radicle, with to aldehyde and a hydrohalide 01 a compound havinu a single amino nitrogen atom. said atom bedrouen and otherwise Joined only to hydrocarbon rndlcles.

8.. The process oi preparing amino ketones which comprises reacting a compound having the structural iormula (OHahOHgB (omnoncootomhommnoomowmnooc(om :on,n

group consisting of an amino-nitrogen-containin; compound and a hydrohalide thereof, the aminmnitrogen-containing compound having a single nitrogen atom, said atom being trivalent andrattached-ito at least one hydrogen and other-- iii. Process as set forth in claim 2 in which the amino-nitrogen compound is ammonia.

11; Process as set forth in claim 2, in which the amino-nitrogen compound is an amine having at least one amino-hydrogen atom.

12. The reaction products set forth in claim 4 in which the lretone is di-isopropyl ketone.

13. The reaction products set forth in claim 4 in which the amino-nitrogen compound is ammonia.

1d. The reaction products set forth in claim 4 in which the amino 'nitrogen compound is an amine having at least one amino-hydrogen atom.

15. Compounds having the general formula RC 0 C(CHahCHaN where R, is a monovalent hydrocarbon radical and R1 and R2 are selected from the group consisting of hydrogen and monovalent hydrocarbon radicals.

16. A compound of the formula R1 omucnooo omnonm where R1 and R2 are radicals of the type set forth in claim 15.

17. Compounds having the general formula Rooowmnommmomc(crime0cwnmomN where R, R1, and R2 are radicals of the type set iorth in claim 15. v V 18. A compound or the iormula radicals of the type set where R1 and R2 are forth in claim 15.

19. A compound of the formula ona icncooccnmcrnnncrn 20. A compound of the formula (CH3) :CHCOC(CH3) 2CH2NHCH2C- (CH3) 2COC(CH3) 2CH2NHCH3 21. compound of the formula rcmncncocwmncnimn RALPH A. JACOBSON. 

